Simvastatin attenuates angiotensin II‑induced inflammation and oxidative stress in human mesangial cells

Zhang,Fengxiang; Sun,Dapeng; Chen,Junjiang; Guan,Ning; Huo,Xiaochuan; Xi,Huanjiu

doi:10.3892/mmr.2014.2871

Simvastatin attenuates angiotensin II‑induced inflammation and oxidative stress in human mesangial cells

Authors:
- Fengxiang Zhang
- Dapeng Sun
- Junjiang Chen
- Ning Guan
- Xiaochuan Huo
- Huanjiu Xi
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Affiliations: Department of Anatomy, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Cardiovascular Surgery, The First Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: November 5, 2014 https://doi.org/10.3892/mmr.2014.2871
Pages: 1246-1251

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Abstract

Chronic kidney disease (CKD) is an intractable disease in which inflammation and oxidative stress are important. In the present study, the effect of simvastatin on inflammation and oxidative stress induced by angiotensin II (Ang II) in human mesangial cells (HMCs) and its corresponding mechanism was examined. In the in vitro experiment, HMCs were pretreated either without additives (control group) or with simvastatin at different concentrations (0, 0.1, 1 or 10 µM) for 1 h and were then stimulated by Ang II (1 µM) for 24 h. Following stimulation, the cells were collected for analysis using quantitative polymerase chain reaction, western blotting and dihydroethidium staining. The supernatant of the cells was collected and analyzed using an enzyme‑linked immunosorbent assay. The results demonstrated that simvastatin suppressed the increased mRNA expression of monocyte chemoattractant protein‑1, tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 and the content of reactive oxygen species induced by Ang II in a dose‑dependent manner. In addition, simvastatin decreased the protein expression of cyclooxygenase‑2 (COX‑2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and protein kinase C (PKC) as well as the content of prostaglandin E2 and the phosphorylation level of nuclear factor‑κB (NF‑κB) p65 in a dose‑dependent manner. Furthermore, simvastatin significantly increased the protein expression of peroxisome proliferator‑activated receptor γ (PPARγ). Therefore, simvastatin suppressed inflammation and oxidative stress in Ang II‑stimulated HMCs via COX‑2, PPARγ, NF‑κB, NADPH oxidase and PKCs, thereby exerting a protective effect on CKD.

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